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S iah2‐deficient mice show impaired skin wound repair
Author(s) -
Musyoka James N.,
Liu Mira C.P.,
Pouniotis Dodie S.,
Wong Christina S.F.,
Bowtell David D.,
Little Peter J.,
Getachew Robel,
Möller Andreas,
Darby Ian A.
Publication year - 2013
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12045
Subject(s) - wound healing , myofibroblast , hypoxia inducible factors , hypoxia (environmental) , ubiquitin ligase , cancer research , fibrosis , microbiology and biotechnology , biology , fibroblast , immunology , pathology , chemistry , ubiquitin , medicine , cell culture , biochemistry , genetics , organic chemistry , oxygen , gene
Hypoxia is associated with the dermal wound healing process and hypoxia signaling is presumed to be crucial for normal wound repair. The S iah2 ubiquitin ligase controls the abundance of hypoxia‐inducible factor‐1 alpha, and loss of S iah2 results in destabilization of hypoxia‐inducible factor‐1 alpha under hypoxia. Utilizing S iah2 −/− mice we demonstrate that cutaneous wound healing is impaired in these mice. Wounds in S iah2 −/− mice heal slower and are associated with delayed induction of myofibroblast infiltration and reduced collagen deposition. This coincides with delayed angiogenesis and reduced macrophage infiltration into the wounds of S iah2 −/− mice. We furthermore demonstrate that primary S iah2 −/− dermal fibroblasts have reduced migratory capacities and produce less collagen than wild‐type fibroblasts. Additionally, S iah2 −/− fibroblasts showed conserved responses to transforming growth factor‐β at the receptor level (p S mad 2 C activation) but reduced responses downstream. Together, our data show, for the first time, that S iah2 is involved as a positive regulator in the wound healing response. Understanding the role of hypoxia signaling in tissue repair and fibrosis and interference with the hypoxia signaling pathway via regulation of S iah2 may provide new targets for clinical regulation of fibrosis and scarring.